Paper de la quinasa IKKalpha al càncer colorectal

Prèviament havíem identificat la presència d’una forma de l’IKKα de 45kD que s’expressa específicament en el nucli de les cèl.lules de cancer colorectal. A més havíem demostrat que aquesta forma estava fosforilada la qual cosa suggereix que es tracta d’una forma activa d’IKKa. Un dels objectius que ens varem plantejar va ser determinar el mecanisme per el qual es generava aquesta forma de la quinasa. Mitjançant eines bioinformàtiques hem identificat possibles llocs de processament proteolític en la seqüència d’IKKα que podrien ser responsables de generar el fragment de 45kD present en les cèl.lules tumorals. Després, hem demostrat que les proteases identificades in silico són capaces de processar IKKa in vitro, específicament en els llocs predits. S’ha pogut constatar, mitjançant la mutació dels possibles llocs de processament, que només un dels llocs identificats bioinformàticament corresponent a Cathepsin B/L era funcional in vitro, mentre que els altres llocs predits no ho eren. D’igual manera, l’expressió ectòpica de la Cathepsin B o L és capaç de produïr el processament d’IKKα. Pel contrari, la inhibició de l’activitat de la proteasa mitjançant inhibidors específics és capaç de bloquejar el processament d’IKKa en cèl.lules tumorals. Finalment, hem demostrat que els nivells de la Cathepsin B i L, proteases identificades com a responsables de processar IKKa es troben sobre-expressades en la majoria de les mostres humanes de càncer de colon analitzades comparat amb el teixit normal adjacent del mateixos pacients.

Estudi comparatiu de detecció de Virus del Papiloma Humà entre pell psoriàsica i pell normal.

Existeix un debat continu sobre la rellevància del Virus del papiloma humà (VPH) en l’etiopatogènia de la psoriasi. S’ha reportat un elevat percentatge de detecció de VPH en pacients psoriàsics, sobretot el VPH5 i 36, suggerint que podrien correspondre a l’antigen causal de la cascada inmunològica. El propòsit de l’estudi és utilitzar un mètode ampli per a la detecció d’ADN tant de beta com gamma-papilomavirus en 30 biòpsies de pell psoriàsica i 30 biòpsies de pell sana. Avaluarem si els VPH són detectats de forma més freqüent en pell psoriàsica en comparació amb pell sana, i quins són els VPH específics més sobreexpresats.

Address by Michea¡l Martin to the Conference - Legislating for Tobacco Free Society

Thank you Chairman I would like to extend a warm welcome to our keynote speakers, David Byrne of the European Commission, Derek Yach from the World Health Organisation, and Paul Quinn representing Congressman Marty Meehan who sends his apologies. When we include the speakers who will address later sessions, this is, undoubtedly, one of the strongest teams that have been assembled on tobacco control in Europe. The very strength of the team underlines what I see as a shift – a very necessary shift – in the way we perceive the tobacco issue. For the last twenty years, we have lived out a paradox. It isn´t a social side issue. I make no apology for the bluntness of what I´m saying, and will come back, a little later, to the radicalism I believe we need to bring – nationally – to this issue. For starters, though, I want to lay it on the line that what we´re talking about is an epidemic as deadly as any suffered by human kind throughout the centuries. Slower than some of those epidemics in its lethal action, perhaps. But an epidemic, nonetheless. According to the World Health Organisation tobacco accounted for just over 3 million annual deaths in 1990, rising to 4.023 million annual deaths in 1998. The numbers of deaths due to tobacco will rise to 8.4 million in 2020 and reach roughly 10 million annually by 2030. This is quite simply ghastly. Tobacco kills. It kills in many different ways. It kills increasing numbers of women. It does its damage directly and indirectly. For children, much of the damage comes from smoking by adults where children live, study, play and work. The very least we should be able to offer every child is breathable air. Air that doesn´t do them damage. We´re now seeing a global public health response to the tobacco epidemic. The Tobacco Free Initiative launched by the World Health Organisation was matched by significant tobacco control initiatives throughout the world. During this conference we will hear about the experiences our speakers had in driving these initiatives. This Tobacco Free Initiative poses unique challenges to our legal frameworks at both national and international levels; in particular it raises challenges about the legal context in which tobacco products are traded and asks questions about the impact of commercial speech especially on children, and the extent of the limitations that should be imposed on it. Politicians, supported by economists and lawyers as well as the medical profession, must continue to explore and develop this context to find innovative ways to wrap public health considerations around the trade in tobacco products – very tightly. We also have the right to demand a totally new paradigm from the tobacco industry. Bluntly, the tobacco industry plays the PR game at its cynical worst. The industry sells its products without regard to the harm these products cause. At the same time, to gain social acceptance, it gives donations, endowments and patronage to high profile events and people. Not good enough. This model of behaviour is no longer acceptable in a modern society. We need one where the industry integrates social responsibility and accountability into its day-to-day activities. We have waited for this change in behaviour from the tobacco industry for many decades. Unfortunately the documents disclosed during litigation in the USA and from other sources make very depressing reading; it is clear from them that any trust society placed in the tobacco industry in the past to address the health problems associated with its products was misplaced. This industry appears to lack the necessary leadership to guide it towards just and responsible action. Instead, it chooses evasion, deception and at times illegal activity to protect its profits at any price and to avoid its responsibilities to society and its customers. It has engaged in elaborate ´spin´ to generate political tolerance, scientific uncertainty and public acceptance of its products. Legislators must act now. I see no reason why the global community should continue to wait. Effective legal controls must be laid on this errant industry. We should also keep these controls under review at regular intervals and if they are failing to achieve the desired outcomes we should be prepared to amend them. In Ireland, as Minister for Health and Children, I launched a comprehensive tobacco control policy entitled “Towards a Tobacco Free Society“. OTT?Excessive?Unrealistic? On the contrary – I believe it to be imperative and inevitable. I honestly hold that, given the range of fatal diseases caused by tobacco use we have little alternative but to pursue the clear objective of creating a tobacco free society. Aiming at a tobacco free society means ensuring public and political opinion are properly informed. It requires help to be given to smokers to break the addiction. It demands that people are protected against environmental tobacco smoke and children are protected from any inducement to experiment with this product. Over the past year we have implemented a number of measures which will support these objectives; we have established an independent Office of Tobacco Control, we have introduced free nicotine replacement therapy for low-income earners, we have extended our existing prohibitions on tobacco advertising to the print media with some minor derogations for international publications. We have raised the legal age at which a person can be sold tobacco products to eighteen years. We have invested substantially more funds in health promotion activities and we have mounted sustained information campaigns. We have engaged in sponsorship arrangements, which are new and innovative for public bodies. I have provided health boards with additional resources to let them mount a sustained inspection and enforcement service. Health boards will engage new Directors of Tobacco Control responsible for coordinating each health board´s response and for liasing with the Tobacco Control Agency I set up earlier this year. Most recently, I have published a comprehensive Bill – The Public Health (Tobacco) Bill, 2001. This Bill will, among other things, end all forms of product display and in-store advertising and will require all retailers to register with the new Tobacco Control Agency. Ten packs of cigarettes will be banned and transparent and independent testing procedures of tobacco products will be introduced. Enforcement officers will be given all the necessary powers to ensure there is full compliance with the law. On smoking in public places we will extend the existing areas covered and it is proposed that I, as Minister for Health and Children, will have the powers to introduce further prohibitions in public places such as pubs and the work place. I will also provide for the establishment of a Tobacco Free Council to advise and assist on an ongoing basis. I believe the measures already introduced and those additional ones proposed in the Bill have widespread community support. In fact, you´re going to hear a detailed presentation from the MRBI which will amply illustrate the extent of this support. The great thing is that the support comes from smokers and non-smokers alike. Bottom line, Ladies and Gentlemen, is that we are at a watershed. As a society (if you´ll allow me to play with a popular phrase) we´ve realised it´s time to ´wake up and smell the cigarettes.´ Smell them. See them for what they are. And get real about destroying their hold on our people. The MRBI survey makes it clear that the single strongest weapon we have when it comes to preventing the habit among young people is price. Simple as that. Price. Up to now, the fear of inflation has been a real impediment to increasing taxes on tobacco. It sounds a serious, logical argument. Until you take it out and look at it a little more closely. Weigh it, as it were, in two hands. I believe – and I believe this with a great passion – that we must take cigarettes out of the equation we use when awarding wage increases. I am calling on IBEC and ICTU, on employers and trade unions alike, to move away from any kind of tolerance of a trade that is killing our citizens. At one point in industrial history, cigarettes were a staple of the workingman´s life. So it was legitimate to include them in the ´basket´ of goods that goes to make up the Consumer Price Index. It isn´t legitimate to include them any more. Today, I´m saying that society collectively must take the step to remove cigarettes from the basket of normality, from the list of elements which constitute necessary consumer spending. I´m saying: “We can no longer delude ourselves. We must exclude cigarettes from the considerations we address in central wage bargaining. We must price cigarettes out of the reach of the children those cigarettes will kill.” Right now, in the monthly Central Statistics Office reports on consumer spending, the figures include cigarettes. But – right down at the bottom of the page – there´s another figure. Calculated without including cigarettes. I believe that if we continue to use the first figure as our constant measure, it will be an indictment of us as legislators, as advocates for working people, as public health professionals. If, on the other hand, we move to the use of the second figure, we will be sending out a message of startling clarity to the nation. We will be saying “We don´t count an addictive, killer drug as part of normal consumer spending.” Taking cigarettes out of the basket used to determine the Consumer Price Index will take away the inflation argument. It will not be easy, in its implications for the social partners. But it is morally inescapable. We must do it. Because it will help us stop the killer that is tobacco. If we can do it, we will give so much extra strength to health educators and the new Tobacco Control Association. This new organisation of young people who already have branches in over fifteen counties, is represented here today. The young adults who make up its membership are well placed to advise children of the dangers of tobacco addiction in a way that older generations cannot. It would strengthen their hand if cigarettes move – in price terms – out of the easy reach of our children Finally, I would like to commend so many public health advocates who have shown professional and indeed personal courage in their commitment to this critical public health issue down through the years. We need you to continue to challenge and confront this grave public health problem and to repudiate the questionable science of the tobacco industry. The Research Institute for a Tobacco Free Society represents a new and dynamic form of partnership between government and civil society. It will provide an effective platform to engage and mobilise the many different professional and academic skills necessary to guide and challenge us. I wish the conference every success.

Retinal fluorescein contrast arrival time of young patients with the hepatosplenic form of the Schistosomiasis mansoni

Schistosoma mansoni is responsible for lesions that can alter the hemodinamic of the portal venous circulation, lung arterial and venous sistemic systems. Therefore, hemodinamic changes in the ocular circulation of mansonic schistosomotic patients with portal hypertension and hepatofugal venous blood flow is also probable. The purpose of this study was to determine the fluorescein contrast arrival time at the retina of young patients with the hepatosplenic form of schistosomiasis, clinically and surgically treated. The control group included 36 non schistosomotic patients, mean age of 17.3 years, and the case group was represented by 25 schistosomotic patients, mean age of 18.2 years, who were cared for at The University Hospital (Federal University of Pernambuco, Brazil), from 1990 to 2001. They underwent digital angiofluoresceinography and were evaluated for the contrast arrival time at the early retinal venous phase of the exam. Both groups were ophthalmologically examined at the same hospital (Altino Ventura Foundation, Recife, Brazil), using the same technique. There was retardation of the retinal contrast arrival time equal or more than 70 sec in the eyes of three schistosomotic patients (12%) and in none of the control group, however, the mean contrast arrival time between the two groups were not statistically different. These findings lend support to the hypothesis that there could be a delay of the eye venous blood flow drainage.

Carcinoembryonic antigen (CEA): demonstration of a partial identity between CEA and a normal glycoprotein.

The carcinoembryonic antigen of the human digestive tract (CEA), described by Gold as a glycoprotein specific for digestive carcinomatous and foetal tissues, was found to have common antigenic determinants with a glycoprotein of smaller size extracted from normal adult tissues. This observation suggests that only a part of the CEA molecule carries the onco-foetal specificity. It also has practical implications regarding the radioimmunoassay for CEA used for the diagnosis of certain carcinomas.

Mast cells are dispensable for normal and activin-promoted wound healing and skin carcinogenesis.

The growth and differentiation factor activin A is a key regulator of tissue repair, inflammation, fibrosis, and tumorigenesis. However, the cellular targets, which mediate the different activin functions, are still largely unknown. In this study, we show that activin increases the number of mature mast cells in mouse skin in vivo. To determine the relevance of this finding for wound healing and skin carcinogenesis, we mated activin transgenic mice with CreMaster mice, which are characterized by Cre recombinase-mediated mast cell eradication. Using single- and double-mutant mice, we show that loss of mast cells neither affected the stimulatory effect of overexpressed activin on granulation tissue formation and reepithelialization of skin wounds nor its protumorigenic activity in a model of chemically induced skin carcinogenesis. Furthermore, mast cell deficiency did not alter wounding-induced inflammation and new tissue formation or chemically induced angiogenesis and tumorigenesis in mice with normal activin levels. These findings reveal that mast cells are not major targets of activin during wound healing and skin cancer development and also argue against nonredundant functions of mast cells in wound healing and skin carcinogenesis in general.

Evaluation of cholinesterase level in an endemic population exposed to malathion suspension formulation as a vector control measure

The manuscript describes a study on the blood cholinesterase (ChE) level in an exposed population at different interval of time after spraying with malathion suspension (SRES) use for kala-azar vector control in an endemic area of Bihar, India. The toxicity of a 5% malathion formulation in the form of a slow release emulsified suspension (SRES) was assessed by measuring serum ChE levels in spraymen and in the exposed population.The study showed a significant decrease in ChE levels in the spraymen (p < 0.01) after one week of spraying and in exposed population one week and one month after of spraying (p < 0.01), but was still within the normal range of ChE concentration, one year after spraying, the ChE concentration in the exposed population was the same as prior to spraying (p > 0.01). On no occasion was the decrease in ChE level alarming. A parallel examination of the clinical status also showed the absence of any over toxicity or any behavioural changes in the exposed population. Hence, it may be concluded that 5% malathion slow release formulation, SRES, is a safe insecticide for use as a vector control measure in endemic areas of kala-azar in Bihar, India so long as good personal protection for spraymen is provided to minimize absorption and it can substitute the presently used traditional DDT spray.

Association of human leukocyte antigen DQ1 and dengue fever in a white Southern Brazilian population

Dengue is an infectious disease of viral etiology transmitted by the mosquitoes Aedes aegypti, A. albopictus, and A. scutellaris. It can develop either as a benign form or as a severe hemorrhagic form. Previous work showed an association of the hemorrhagic form with human leukocyte antigens (HLA), suggesting a role of genetic factors in disease susceptibility. Nevertheless, data on HLA association with the classical form of the disease is scarce in literature. Sixty-four patients and 667 normal individuals, living in the state of Paraná, Southern Brazil, were used as test and control group, respectively. The patients developed the disease during a virus 1 dengue outbreak either in Maringá city in 1995 (47) or in Paranavaí city in 1999 (17). The diagnostic was confirmed through serology and/or viral culture. HLA class I and II typing was performed by the classical microlynfocitotoxicity test using monoclonal antisera and fluorobeads. Qui-square statistical analysis confirmed a positive association with HLA-DQ1 (76.6% vs 57.7%; p = 0.005243; pc = 0.026215). HLA-DR1 also presented an increased frequency in the test group, not statistically significant after p correction though (32.8% vs 15.9%; p = 0.005729; pc = 0.080206). In conclusion, genetic factors may play a role on the susceptibility to the classical dengue, virus 1, in the Brazilian population. Further independent studies should be performed in the Brazilian population to confirm these preliminary data.

Subclinical form of the American visceral leishmaniasis

The subclinical form of visceral leishmaniasis (VL) shows nonspecific clinical manifestations, with difficulties being frequently met in its clinical characterization and diagnostic confirmation. Thus, the objective of the present study was to define the clinical-laboratory profile of this clinical form. A cohort study was conducted in the state of Maranhão, Brazil, from January/1998 to December/2000, with monthly follow-up of 784 children aged 0-5 years. Based on the clinical-laboratory parameters reported in the literature, four categories were established, with the children being classified (according to their clinical-evolutive behavior) as asymptomatic (N = 144), as having the subclinical form (N = 33) or the acute form (N = 12) or as subjects "without VL" (N = 595). Multiple discriminant analysis demonstrated that the combination of fever, hepatomegaly, hyperglobulinemia, and increased blood sedimentation rate (BSR) can predict the subclinical form of VL as long as it is not associated with splenomegaly or leukopenia. Subjects with the subclinical form did not show prolonged or intermittent evolution or progression to the acute form of VL. Subclinical cases have a profile differing from the remaining clinical forms of VL, being best characterized by the combination of fever, hepatomegaly, hyperglobulinemia, and increased BSR.

Escherichia coli variants in periprosthetic joint infection: diagnostic challenges with sessile bacteria and sonication.

The diagnostic yield of prosthetic joint-associated infection is hampered by the phenotypic change of bacteria into a sessile and resistant form, also called biofilm. With sonication, adherent bacteria can be dislodged from the prosthesis. Species identification may be difficult because of their variations in phenotypic appearance and biochemical reaction. We have studied the phenotypic, genotypic, and biochemical properties of Escherichia coli variants isolated from a periprosthetic joint infection. The strains were collected from synovial fluid, periprosthetic tissue, and fluid from the explanted and sonicated prosthesis. Isolates from synovial fluid revealed a normal phenotype, whereas a few variants from periprosthetic tissue and all isolates from sonication fluid showed different morphological features (including small-colony variants). All isolates from sonication fluid were beta-galactosidase negative and nonmotile; most were indole negative. Because of further variations in biochemical properties, species identification was false or not possible in 50% of the isolates included in this study. In contrast to normal phenotypes, variants were resistant to aminoglycosides. Typing of the isolates using pulsed-field gel electrophoresis yielded nonidentical banding patterns, but all strains were assigned to the same clonal origin when compared with 207 unrelated E. coli isolates. The bacteria were repeatedly passaged on culture media and reanalyzed. Thereafter, most variants reverted to normal phenotype and regained their motility and certain biochemical properties. In addition, some variants displayed aminoglycoside susceptibility after reversion. Sonication of an explanted prosthesis allows insight into the lifestyle of bacteria in biofilms. Since sonication fluid also reveals dislodged sessile forms, species identification of such variants may be misleading.

Acquired auditory agnosia in childhood and normal sleep electroencephalography subsequently diagnosed as Landau-Kleffner syndrome: a report of three cases.

Aim  We report three cases of Landau-Kleffner syndrome (LKS) in children (two females, one male) in whom diagnosis was delayed because the sleep electroencephalography (EEG) was initially normal. Method  Case histories including EEG, positron emission tomography findings, and long-term outcome were reviewed. Results  Auditory agnosia occurred between the age of 2 years and 3 years 6 months, after a period of normal language development. Initial awake and sleep EEG, recorded weeks to months after the onset of language regression, during a nap period in two cases and during a full night of sleep in the third case, was normal. Repeat EEG between 2 months and 2 years later showed epileptiform discharges during wakefulness and strongly activated by sleep, with a pattern of continuous spike-waves during slow-wave sleep in two patients. Patients were diagnosed with LKS and treated with various antiepileptic regimens, including corticosteroids. One patient in whom EEG became normal on hydrocortisone is making significant recovery. The other two patients did not exhibit a sustained response to treatment and remained severely impaired. Interpretation  Sleep EEG may be normal in the early phase of acquired auditory agnosia. EEG should be repeated frequently in individuals in whom a firm clinical diagnosis is made to facilitate early treatment.

Cochrane Short Courses Training Application Form 2011

Application Form for Training Courses on Conducting Systematic Reviews, 2011.

Analysis of prion strains by PrPSc profiling in sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Prion diseases are a group of invariably fatal neurodegenerative disorders affecting humans and a wide range of mammals. An essential part of the infectious agent, termed the prion, is composed of an abnormal isoform (PrPSc) of a host-encoded normal cellular protein (PrPC). The conversion of PrPC to PrPSc is thought to play a crucial role in the development of prion diseases and leads to PrPSc deposition, mainly in the central nervous system. Sporadic Creutzfeldt-Jakob disease (sCJD), the most common form of human prion disease, presents with a marked clinical heterogeneity. This diversity is accompanied by a molecular signature which can be defined by histological, biochemical, and genetic means. The molecular classification of sCJD is an important tool to aid in the understanding of underlying disease mechanisms and the development of therapy protocols. Comparability of classifications is hampered by disparity of applied methods and inter-observer variability. METHODS AND FINDINGS: To overcome these difficulties, we developed a new quantification protocol for PrPSc by using internal standards on each Western blot, which allows for generation and direct comparison of individual PrPSc profiles. By studying PrPSc profiles and PrPSc type expression within nine defined central nervous system areas of 50 patients with sCJD, we were able to show distinct PrPSc distribution patterns in diverse subtypes of sCJD. Furthermore, we were able to demonstrate the co-existence of more than one PrPSc type in individuals with sCJD in about 20% of all patients and in more than 50% of patients heterozygous for a polymorphism on codon 129 of the gene encoding the prion protein (PRNP). CONCLUSION: PrPSc profiling represents a valuable tool for the molecular classification of human prion diseases and has important implications for their diagnosis by brain biopsy. Our results show that the co-existence of more than one PrPSc type might be influenced by genetic and brain region-specific determinants. These findings provide valuable insights into the generation of distinct PrPSc types.